Development of new radioisotope-labeled peptides for effective delivery in cancer therapy

• Project/Area Number: 15K19810
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: Oshima Nobuhiro 北海道医療大学, 薬学部, 助教 (80508648)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 放射性医薬品 / octreotide / 腎臓 / がん / 体内動態 / インジウム-111 / アイソトープ内用療法 / 腫瘍 / ペプチド / 薬物動態 / ソマトスタチン / アイソトープ治療 / オクトレオチド / イットリウム-90 / 腫瘍集積 / インジウム

Outline of Final Research Achievements

Recently, Radioisotope (RI)-labeled peptides have been studied as therapeutic agents for cancer treatment. However, their clinical applications are difficult because of non-specific long-lasting accumulation of radioactivity in the kidney. To resolve this problem, we demonstrated the renal accumulation could be reduced by introducing a negative charge to peptide moiety with acidic amino acid. In addition, we also found that the elongation of amino acids to original peptide sequences dramatically increased tumor accumulation of radioactivity. In this study, we successfully developed a new RI-labeled peptide derivative which showed both lower renal radioactivity and higher tumor radioactivity by chemical modifications of the peptide sequence.

Research Products

• [Journal Article] 111In-DTPA-D-Phe-1-Asp0-D-Phe1-octreotide exhibits higher tumor accumulation and lower renal radioactivity than 111In-DTPA-D-Phe1-octreotide (2017)
  • Author(s): Nobuhiro Oshima, Hiromichi Akizawa, Hirotake Kitaura, Hidekazu Kawashima, Songji Zhao, Yan Zhao, Ken-ichi Nishijima, Yoji Kitamura, Yasushi Arano, Yuji Kuge, Kazue Ohkura
  • Journal Title: Nuclear Medicine and Biology Volume: 54 Pages: 18-26
  • DOI: 10.1016/j.nucmedbio.2017.07.002
  • Peer Reviewed
• [Journal Article] Redesign of negatively charged 111In-DTPA-octreotide derivative to reduce renal radioactivity (2017)
  • Author(s): Oshima N., Akizawa H., Kawashima H., Zhao S., Zhao Y., Nishijima K. I., Kitamura Y., Arano Y., Kuge Y. and Ohkura K.
  • Journal Title: Nuclear medicine and biology Volume: 48 Pages: 16-25
  • DOI: 10.1016/j.nucmedbio.2017.01.006
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 111In-DTPA-L-Phe-1-Asp0-D-Phe1-octreotide の正常マウスでの体内動態および in vitro 腫瘍集積性の評価 (2018)
  • Author(s): 大島伸宏, 亀山裕司, 鹿内浩樹, 北浦廣剛, 秋澤宏行, 大倉一枝
  • Organizer: 日本薬学会 第138年会
• [Presentation] New 111In-labeled octreotide derivatives with increased specific tumor uptake (2017)
  • Author(s): Nobuhiro Oshima
  • Organizer: CIS Workshop 2017 2nd
  • Int'l Joint Research / Invited
• [Presentation] 111In-DTPA-D-Phe－1-Asp0-D-Phe1-octreotide の 高い腫瘍集積性の原因解明に向けた N 末端伸長 octreotide の構 活性相関研究 (2016)
  • Author(s): 大島伸宏, 近江悠, 近藤史博, 河嶋秀和, 秋澤宏行, 大倉一枝
  • Organizer: 第16回 放射性医薬品・画像診断薬研究会
  • Place of Presentation: 京都勧業館「みやこめっせ」 (京都府、京都市)
  • Year and Date: 2016-10-01
• [Presentation] 111In-DTPA-オクトレオチドの錯構造に基づく幾何異性体の相互変換と受容体親和性に関する検討 (2015)
  • Author(s): 大島伸宏、河嶋秀和、秋澤宏行、久下裕司、大倉一枝
  • Organizer: 第55回 日本核医学会学術総会
  • Place of Presentation: ハイアットリージェンシー東京
  • Year and Date: 2015-11-05
• [Remarks] 北海道医療大学 薬学部 生命物理科学講座 放射薬品化学教室 web site
  • URL: http://www3.hoku-iryo-u.ac.jp/courses/1/008/index.html
• [Remarks] 研究代表者の Research map ページ
  • URL: https://researchmap.jp/31415926/
• [Remarks] 北海道医療大学講座・教員案内 生命物理科学 (放射薬品化学) 研究実績
  • URL: http://www3.hoku-iryo-u.ac.jp/courses/1/008/research.html